No abstract

Understanding the interactions between herpesviruses and their host cells and also the interactions between neoplastically transformed cells and the host immune system is fundamental to understanding the mechanisms of herpesvirus oncology. However, this has been difficult as no animal models of herpesvirus-induced oncogenesis in the natural host exist in which neoplastically transformed cells are also definitively identified and may be studied in vivo.

Flow cytometric and immunocytochemical techniques were used to quantify, identify and locate Marek's disease herpesvirus (MDV)-infected lymphocytes in lymphoid organs of infected chickens, by expression of the virus antigen pp38. Two closely related lines of chicken, one susceptible to Marek's disease (line 7 2 ) and another resistant (line 6 1 ), were infected at 2 weeks of age and compared at 10 sampling times between 0 and 50 days post-infection. In both lines 6 1 and 7 2 , pp38 M lymphocytes were detected at 4-6 days in the spleen, thymus and bursa. pp38 M cells could not be detected from day 8 onwards. In both lines, pp38 M lymphocytes were located in the peri-ellipsoidal area of the spleen, the medulla of the thymic lobes

Abstract. Genotype-dependent differences in Marek's disease (MD) susceptibility were identified using 14-day-old line N and 6 1 (resistant) and 15I and 7 2 (susceptible) inbred chickens infected with HPRS-16 MD virus (MDV). All line 7 2 chickens developed progressive MD. Line 15I had fluctuating MD-specific clinical signs and individuals recovered. A novel histologic scoring system enabled indices to be calculated for lymphocyte infiltration into nonlymphoid organs. All genotypes had increased mean lesion scores (MLSs) and mean total lesion scores after MDV infection. These differed quantitatively and qualitatively between the genotypes. Lines 6 1 and 7 2 had a similar MLS distribution in the cytolytic phase, although scores were greater in line 7 2 . At the time lymphomas were visible in line 7 2 , histologic lesions in line 6 1 were regressing. AV37 ϩ cells were present in similar numbers in all genotypes in the cytolytic phase, suggesting that neoplastically transformed cells were present in all genotypes regardless of MD susceptibility. After the cytolytic phase, AV37ϩ cell numbers increased in lines 7 2 and 15I but decreased in lines 6 1 and N. In the cytolytic and latent phases, in all genotypes, most infiltrating cells were CD4 ϩ . After this time, line 7 2 and 15I lesions increased in size and most cells were CD4 ϩ ; line 6 1 and N lesions decreased in size and most cells were CD8ϩ . In all genotypes, AV37 immunostaining was weak in lesions with many CD8 ϩ cells, suggesting that AV37 antigen expression or AV37 ϩ cells were controlled by CD8 ϩ cells. The rank order, determined by clinical signs and pathology, for MD susceptibility (highest to lowest) was 7 2 Ͼ 15I Ͼ 6 1 Ͼ N.

The chB6 molecule is expressed on chicken B cells throughout most of their development, as well as on some non-lymphoid cells. It has long been used as an allotypic marker in important studies of B-cell development, though its function is unknown. We isolated a chB6 cDNA by expression cloning and sequenced two further alleles following polymerase chain reaction amplification. The results show that chB6 is a typical type I transmembrane protein, highly glycosylated in the extracellular region and carrying a large intracellular region. It has no recognizable similarity to known mammalian molecules and thus represents a unique B-cell marker. Its presence in chickens may be related to differences in the properties of B-cell development between chickens and mammalian species. The sequences of the different alleles of this gene revealed a higher level of polymorphism than expected. A restriction fragment length polymorphism linked to the CHB6 gene has been used to determine its location on the linkage map of the chicken genome, which will allow the definitive evaluation of reported associations with disease resistance.